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74 Cards in this Set
- Front
- Back
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Accounts for __% of ESRD in the US
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Accounts for 51% of ESRD in the US
-38% diabetic nephropathy -13% nondiabetic glomerular disease |
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Definition of glomerulonephritis
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Intraglomerular inflammation
Cellular proliferation Hematuria Excludes nonproliferative disorders |
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Glomerulonephritis refers to
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Refers to that variety of kidney disease in which proliferation and inflammation of the glomerulus is secondary to an immunologic mechanism.
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Glomerulonephritis Presentation of GN
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Presentation of GN varies from microscopic asymptomatic hematuria or proteinuria to acute nephritis, to rapidly progressive nephritis.
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Glomerulonephritis Characterized by abrupt onset
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of hematuria, proteinuria, with rise in BUN/creatinine levels
Frequently hypertensive Frequently develop peripheral edema Sediment contains RBC’s or RBC casts Variable clinical course Variable proteinuria; generally less than 3.5g/day |
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nephrotic syndrome
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onset- insidious
edema- ++ BP- normal JVP- normal/low Proteinurea- ++++ Hematuria- may/may not Red class casts- NO Serum albumin- LOW |
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nephritic syndrome
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onset- abrupt
edema- ++++ BP- raised JVP- Raised Proteinurea- ++ low Hematuria-+++ Red class casts- present Serum albumin- normal/slightly reduced |
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Focal Proliferative Glomerulonephritis
include what disease types? |
IgA nephropathy
Henoch-Schonlein purpura Lupus nephritis (class II and III) Heriditary nephritis (Alport’s) |
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Diffuse Proliferative Glomerulonephritis
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Poststreptococcal glomerulonephritis
Bacterial endocarditis Lupus nephritis (Class IV) Membranoproliferative glomerulonephritis Crescentic glomerulonephritis Vasculitis |
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Workup of Glomerulonephritis
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General blood work to include lytes, bun, creatinine
CBC to evaluate for anemia and platelets Urinalysis to include microscopic exam Serum and urine protein electrophoresis Serum albumin and lipid levels Serologic studies |
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Serology for GN
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ANCA levels for Wegener’s and systemic vasculitis
ANA for lupus AntiGBM- Goodpasture’s IgA/C3 ratio for IgA nephropathy(greater than 4) Increased levels of abnormally glycosolated IgA ASO titer, C3, C4, Hepatitis profile, HIV Above generally not definitive; will frequently require renal biopsy |
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Laboratory Tests - Complements-normal level
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Normal serum complement level
Systemic diseases: a. Vasculitis b. Henoch-Schonlein purpura Renal diseases a. IgA nephropathy b. Idiopathic rapidly progressive glomerulonephritis c. Anti-GBM disease d. IC disease |
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Laboratory Tests - Complements-low level
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Low serum complement level
Systemic diseases SLE (75-90%) Subacute bacterial endocarditis (90%) Cryoglobulinemia (85%) Renal diseases Acute poststreptococcal glomerulonephritis (90%) Membranoproliferative glomerulonephritis (90%) |
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IGA Nephropathy
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Most common cause of glomerulonephritis worldwide
Most common in Asians and Caucasians Defined by immune deposits containing IGA 1/3-1/2 of patients present by age 40 Frequently present with macroscopic hematuria after an upper respiratory infection Can be associated with other systemic or viral disease Abnormal glycosylaton causes IGA deposition in the mesangium ESRD occurs in 20% Predictors of poor outcome include proteinuria>1g, hypertension, elevated creatinine, persistent microscopic hematuria, and early onset Treatment with ACE/ARB, ?fish oil and possibly steroids |
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Henoch-Schonlein Purpura
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Systemic” IgA nephropathy
Arthralgias Purpura Abdominal pain Gastrointestinal bleeding Hematuria |
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Postinfectious Glomerulonephritis
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Clinical presentation
Children 2-10 years, occasionally in adults Uncommon over age 40 (< 10%) Symptoms develop 7 days to 12 weeks after the infection Low complement levels (C3 and CH50) Spontaneous recovery is the rule Hematuria can persist 6 months Proteinuria, mild can persist years Can be nephrotic Treat with BP agents, antibiotics and supportive care |
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Rapidly Progressive Glomerulonephritis
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Clinical syndrome
Glomerulonephritis (nephritic syndrome) Rapid decline in renal function Rare – 2-4% of all glomerulonephritis Pathologic hallmark – crescents or proliferating epithelial cells of Bowman’s capsule Without treatment patients can progress to ESRD in weeks Classified based on presence or absence of immune complexes |
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Rapidly Progressive Glomerulonephritis
subdivision |
Subdivided into three types based on on immunofluorescence findings
AntiGBM Pauci-immune Immune complex disease |
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Immune complex mediated:
Rapidly Progressive Glomerulonephritis type of diseases: |
Henoch-Schonlein purpura
Cryoglobulinemia (often associated with hepatitis C) Lupus nephritis Acute postinfectious glomerulonephritis Bacterial endocarditis Hypersensitivity vasculitis |
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Direct antibody attack mediated
Rapidly Progressive Glomerulonephritis |
Anti-GBM disease/Goodpasture’s syndrome
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Pauci-immune (ANCA associated)
Rapidly Progressive Glomerulonephritis |
Wegener’s granulomatosis
Microscopic polyarteritis Churg-Straus syndrome |
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Anti-GBM Disease
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Clinical presentation:
Bimodal age distribution (3rd and 6th decades) Uncommon- 1-2cases/million Less than 10% of cresenteric GN seen on biopsy 60-70% present with pulmonary hemorrhage Pulmonary infiltrates Systemic symptoms - malaise, fatigue, anorexia, weight loss, arthralgias, myalgias Caucasians Rare in African-Americans Also known as Goodpasture’s syndrome Young men generally present with pulmonary renal syndrome Older women frequently with renal limited disease Smoking predisposes to pulmonary hemorrhage Hematuria, dysmorphic red cells, RBC casts noted Diagnosis based on clinical suspicion and anti-GBM circulating Pathogenesis Antibodies develop against 3 chain type IV collagen in GBM Linear deposition of IgG along GBM Antibodies detected by ELISA ANCA found in ~30% of patients Outcome poor without therapy Treatment Corticosteroids alone insufficient Cyclophosphamide Plasma exchange with albumin 14 days Renal recovery rare if patients present needing dialysis less than 15% Key to achieving dialysis free survival is intervening before creatinine rises above 5.7 |
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Anti-GBM Disease
TX |
Outcome poor without therapy
Treatment Corticosteroids alone insufficient Cyclophosphamide Plasma exchange with albumin 14 days Renal recovery rare if patients present needing dialysis less than 15% Key to achieving dialysis free survival is intervening before creatinine rises above 5.7 |
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Pathogenesis
Anti-GBM Disease |
Antibodies develop against 3 chain type IV collagen in GBM
Linear deposition of IgG along GBM Antibodies detected by ELISA ANCA found in ~30% of patients |
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Wegener’s Granulotmatosis
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Necrotizing vasculitis involving small blood vessels
Classically involves the kidney, upper and lower respiratory tract Microscopic exam reveals necrotizing granulomatous vasculitis Middle age or elderly adults Constitutional symptoms common C-ANCA positive(PR3-ANCA) Hemoptysis is number one cause of death short term Infection long term cause of death Requires lung, upper respiratory tract or renal biopsy for Dx Renal biopsy reveals cresenteric GN Treatment with cytotoxic agents and steroids |
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Membranoproliferative Glomerulonephritis
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Diffuse proliferation of mesangial cells extending into capillary wall
Mesangial and endothelial cell proliferation Divided into several types based on EM Type I MPGN- most common form of the disease Subendothelial deposits Deposition of immunoglobulin and C3 Patients may present with either nephrotic or nephritic syndrome RPGN or more benign course Infection with Hepatitis B or C are the most common causes Decreased C4 |
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MPGN- type 2
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Type II MPGN often caused dense deposit disease
Decreased C3 C3 nephritic factor circulating in serum Frequently resistant to therapy |
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MPGN- type 3
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Type III has subendothelial and subepithelial deposits
Associated with IgA nephropathy and rarel Hepatitis C Generally resistant to steroids |
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Systemic Lupus Erythematosis**
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Complex multisystem autoimmune disease
11 criteria – 4 present for diagnosis Kidney is most common organ involved (50-75%) Females > Males African-Americans have higher rates of lupus nephritis and worse renal survival Clinical spectrum Mild urinary abnormalities Acute and chronic kidney failure Usually develops within 3 years Pathogenesis of renal involvement Histone-DNA complex – planted antigen Anti-dsDNA antibodies eluted from nephritic kidneys WHO recognizes 6 classes |
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Classification of Lupus Nephritis
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Class I “normal”
Class II variable mesangial hyper- cellularity and immune deposits Class III focal proliferative glomerulonephritis Class IV diffuse proliferative glomerulonephritis Class V membranous nephropathy Class VI chronic glomerulosclerosis |
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Lupus Nephritis TX
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10-20% mesangial or focal proliferative
40-60% diffuse proliferative 10-20% membranous nephropathy Treatment Corticosteroids Azathioprine Cyclophosphamide Mycophenolate |
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Thrombotic Microangiopathies
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Characterized by formation of platelet microthrombi, thrombocytopenia and microangiopathic hemolytic anemia
Can lead to TTP or HUS Overlap between the diseases HUS can develop sporadically or from exposure to E. Coli O-157 TTP and HUS can be associated with other syndromes and medications including plavix, cyclosporin, tacrolimis Treatment is supportive and with palsma exchange |
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Clinical Features of the Thrombotic Microangiopathies
draw table |
Glomerulonephritis lecture 4 from Oxman ppt 58
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Evaluation of Glomerulonephritis
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History and exam
Urinalysis – blood, protein and dysmorphic rbc’s +/- rbc casts Complements Additional serology as dictated by presentation |
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Summary-main points
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Glomerular disease is an important cause of CKD and ESRD.
Patients can present with a variety of clinical syndromes. A good history, exam and certain lab tests in conjunction with renal biopsy can often lead to a diagnosis. |
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Refers to that variety of kidney disease in which proliferation and inflammation of the glomerulus is secondary to an immunologic mechanism.
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GN
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Presentation varies from microscopic asymptomatic hematuria or proteinuria to acute nephritis, to rapidly progressive nephritis
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GN
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Characterized by abrupt onset of hematuria, proteinuria, with rise in BUN/creatinine levels
Frequently hypertensive Frequently develop peripheral edema Sediment contains RBC’s or RBC casts Variable clinical course Variable proteinuria; generally less than 3.5g/day |
GN
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IgA nephropathy
Henoch-Schonlein purpura Lupus nephritis (class II and III) Heriditary nephritis (Alport’s) They are all type of: |
Focal Proliferative Glomerulonephritis (FPGN)
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Poststreptococcal glomerulonephritis
Bacterial endocarditis Lupus nephritis (Class IV) Membranoproliferative glomerulonephritis Crescentic glomerulonephritis Vasculitis They are all type of: |
Diffuse Proliferative Glomerulonephritis
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ANCA serology levels for ___ and ___
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Wegener’s and systemic vasculitis
all GN |
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ANA serology for ___
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lupus
GN |
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AntiGBM serology for ___
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Goodpasture’s
GN |
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IgA/C3 ratio serology for ____
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IgA nephropathy
GN |
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Frequently present with macroscopic hematuria after an upper respiratory infection
Can be associated with other systemic or viral disease Most common in Asians and Caucasians 1/3-1/2 of patients present by age 40 |
IgA nephropathy
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IGA Nephropathy TX
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Treatment with ACE/ARB, ?fish oil and possibly steroids
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Arthralgias
Purpura Abdominal pain Gastrointestinal bleeding Hematuria |
“Systemic” IgA nephropathy
Henoch-Schonlein Purpura |
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Children 2-10 years, occasionally in adults
Uncommon over age 40 (< 10%) Symptoms develop 7 days to 12 weeks after the infection Low complement levels (C3 and CH50) Spontaneous recovery is the rule Hematuria can persist 6 months Proteinuria, mild can persist years Can be nephrotic Treat with BP agents, antibiotics and supportive care |
Postinfectious Glomerulonephritis
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Rapid decline in renal function
crescents or proliferating epithelial cells of Bowman’s capsule Without treatment patients can progress to ESRD in weeks Classified based on presence or absence of immune complexes |
Rapidly Progressive Glomerulonephritis
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Rapidly Progressive Glomerulonephritis 3 types:
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AntiGBM
Pauci-immune Immune complex disease |
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Henoch-Schonlein purpura
Cryoglobulinemia (often associated with hepatitis C) Lupus nephritis Acute postinfectious glomerulonephritis Bacterial endocarditis Hypersensitivity vasculitis All types of: |
Immune complex mediated:
Rapidly Progressive Glomerulonephritis |
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Anti-GBM disease/Goodpasture’s syndrome
type of: |
Direct antibody attack mediated
Rapidly Progressive Glomerulonephritis |
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Wegener’s granulomatosis
Microscopic polyarteritis Churg-Straus syndrome |
Pauci-immune (ANCA associated)
Rapidly Progressive Glomerulonephritis |
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Bimodal age distribution (3rd and 6th decades)
Uncommon- 1-2cases/million Less than 10% of cresenteric GN seen on biopsy 60-70% present with pulmonary hemorrhage Pulmonary infiltrates Systemic symptoms - malaise, fatigue, anorexia, weight loss, arthralgias, myalgias Caucasians |
Anti-GBM Disease
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Systemic symptoms - malaise, fatigue, anorexia, weight loss, arthralgias, myalgias
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Anti-GBM Disease
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Young men generally present with pulmonary renal syndrome
Older women frequently with renal limited disease Smoking predisposes to pulmonary hemorrhage Hematuria, dysmorphic red cells, RBC casts noted Diagnosis based on clinical suspicion |
Anti GBM Disease
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Anti-GBM Disease
TX |
Treatment
Corticosteroids alone insufficient Cyclophosphamide Plasma exchange with albumin 14 days Renal recovery rare if patients present needing dialysis less than 15% Key to achieving dialysis free survival is intervening before creatinine rises above 5.7 |
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Necrotizing vasculitis involving small blood vessels
Classically involves the kidney, upper and lower respiratory tract Microscopic exam reveals necrotizing granulomatous vasculitis Middle age or elderly adults Constitutional symptoms common |
Wegener’s Granulotmatosis
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Wegener’s Granulotmatosis
TX |
Treatment with cytotoxic agents and steroids
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C-ANCA positive(PR3-ANCA)
Hemoptysis is number one cause of death short term Infection long term cause of death Requires lung, upper respiratory tract or renal biopsy for Dx Renal biopsy reveals cresenteric GN |
Wegener’s Granulotmatosis
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most common form of the disease
Subendothelial deposits Deposition of immunoglobulin and C3 Patients may present with either nephrotic or nephritic syndrome RPGN or more benign course Infection with Hepatitis B or C are the most common causes Decreased C4 |
Membranoproliferative Glomerulonephritis
TYPE 1 |
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Infection with Hepatitis B or C are the most common causes
Decreased C4 |
Membranoproliferative Glomerulonephritis
TYPE 1 |
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often caused dense deposit disease
Decreased C3 C3 nephritic factor circulating in serum Frequently resistant to therapy |
Membranoproliferative Glomerulonephritis
TYPE 2 |
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Subendothelial and subepithelial deposits
Associated with IgA nephropathy and rarel Hepatitis C Generally resistant to steroids |
Membranoproliferative Glomerulonephritis
TYPE 3 |
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Complex multisystem autoimmune disease
11 criteria – 4 present for diagnosis Kidney is most common organ involved (50-75%) Females > Males African-Americans have higher rates and worse renal survival |
Systemic Lupus Erythematosis
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Mild urinary abnormalities
Acute and chronic kidney failure Usually develops within 3 years |
LUPUS
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variable mesangial hyper-cellularity and immune deposits
What class of lupus? |
class 2
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normal
What class of lupus? |
class 1
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What class of lupus?
focal proliferative glomerulonephritis |
class 3
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What class of lupus?
diffuse proliferative glomerulonephritis |
class 4
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What class of lupus?
membranous nephropathy |
class 5
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What class of lupus?
chronic glomerulosclerosis |
class 6
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Treatment
Lupus |
Corticosteroids
Azathioprine Cyclophosphamide Mycophenolate |
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Thrombotic Microangiopathies
Characterized by formation of |
platelet microthrombi, thrombocytopenia and microangiopathic hemolytic anemia
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